With the advent of proteomic methods, a sudden switch from genomics to proteomics has been observed and indeed, in many cases no definite conclusions can be drawn from the nucleic acid data. Moreover, there is a long and unpredictable way from RNA to protein and differences between neurodegenerative disorders at the mRNA level could not be verified at the protein level. However, proteins carry out the ultimate function and thus the role of proteins is pivotal. Two-dimensional gel electrophoresis with in-gel digestion followed by mass spectrometric methods and subsequent quantification of proteins with specific software allow study of protein expression in a high-throughput way, identifying large series of proteins concomitantly. Furthermore, evaluation of protein expression by proteomic technologies does no longer rely upon the availability and specificity of antibodies. Significant proteomic approaches have been used to study degenerative diseases, including Alzheimers disease, and many protein classes from signalling, metabolic, cytoskeleton, chaperone, antioxidant, and proteasome have been shown to be tentatively involved in pathological mechanisms. The aim of this review is to show what has been studied so far in the area using proteomic approaches, describing methodologies used including their potentials and limitations, and finally what still remains to be done. We are addressing only those methods and results necessary for discussing proteomic observations. The message of this review is that proteomics carries the potential to find important clues for pathogenesis of neurodegenerative diseases and to identify pharmacological targets, once the crucial problems such as analysis of hydrophobic and membrane proteins are solved.